Dataset Information


Interleukin-27 priming of T cells controls Interleukin-17-production in trans via induction of Programmed cell death ligand 1

ABSTRACT: Interleukin (IL)-27 is a key immunosuppressive cytokine that counters T helper 17 (Th17) cell-mediated pathology. To identify mechanisms by which IL-27 might exert its immunosuppressive effect, we analyzed genes in T cells rapidly induced by IL-27. We found that IL-27 priming of naïve T cells upregulated expression of programmed death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)1-dependent manner. When co-cultured with naïve CD4+ T cells, IL-27-primed T cells inhibited the differentiation of Th17 cells in trans through a PD-1-PD-L1 interaction. In vivo, co-administration of naïve TCR transgenic T cells (2D2 T cells) with IL-27-primed T cells expressing PD-L1 inhibited the development of Th17 cells and protected from severe autoimmune encephalomyelitis. Thus, these data identify a suppressive activity of IL-27, by which CD4+ T cells can restrict differentiation of Th17 cells in trans. The roles of IL-6 and IL-27 in naïve CD4+ T cells was investigated by comparing global gene expression by Affymetrix Mouse Genome 430 2.0 Arrays. The functional outcome of STAT proteins was further evaluated by profiling gene expression changes between WT and STAT-deficient T cells in naïve CD4+ T cells with specific stimulation. All condition were done in biological triplicate.

ORGANISM(S): Mus musculus  

SUBMITTER: Hong-Wei Sun   Arian Laurence  Masao Tanaka  Kamran Ghoreschi  Giuseppe Sciumè  Christopher A Hunter  Xiang-Ping Yang  Kiyoshi Hirahara  Christopher Dupont  John J O’Shea  Loise M Francisco  Yuka Kanno  Arlene H Sharpe  Aisling O Hall  Hayato Takahashi  Qian Chen  Golnaz Vahedi 

PROVIDER: E-GEOD-38375 | ArrayExpress | 2012-06-30



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